Category Archives: GERD or reflux

How To Stay Informed

Thanks for following along with the diagnosis and treatment of eosinophilic esophagitis (EoE)–a condition that during my fellowship training in allergy wasn’t even recognized as a cause of abdominal pain. 

Treatment options for EoE are currently:

  • Corticosteroids–both oral and inhaled
  • Dietary avoidance of known allergic triggers, including but not limited to foods 
  • Use of PPIs such as Nexium & Protonix
  •  Treatment principles focus on reducing symptoms and eosinophil counts while, importantly, protecting and preserving quality of life.
  • Maintaining diet and nutrition which is harder than it looks! Don’t forget that restoring growth parameters are also essential for adults as well as in children.
Tastes Great, but NOT less filling!

As with all diseases, treatment is updated constantly, and new recommendations emerge.   As with many inflammatory conditions, steroids work great, but are NOT less filling.  Side effects from steroids are many and any time an alternative is successful, you’re better off.  Remember, topical steroids are fine, it’s the oral systemic absorption of steroids that contributes to the side effect profile.  

 Due to the long-term side effects associated with high dose corticosteroids and a tendency for relapse after discontinuation, this therapy is not first-line outside of using short bursts and tapers for severe symptoms needing urgent relief (eg, critical dysphagia, stricture, dehydration and acute weight loss.

Topical Corticosteroids

Topical corticosteroid are used in EoE through 1 of 2 routes:

  • “Gulping” the expressed actuations of an inhaled device; or
  • Expressing the contents of a nebulizer respule into a cup, forming a thickened slurry by mixing it with sucralose/maltodextrose (Splenda®), and water.

Use in this manner provides “local” or tailored coating of esophageal tissue, at lower doses (220 μg-1 mg per dose). Faubion and colleagues demonstrated that 880 μg/day of swallowed fluticasone propionate or beclomethasone diproprionate resulted in symptomatic improvement in 4/4 pediatric patients Noel and group at the Cincinnati Children’s Medical Center, noted that non-atopic patients had a better response rate to the topical steroid than the atopic patients.  A randomized, controlled trial by Konikoff and colleagues confirmed similar findings independent of pre-treatment eosinophil numbers. 

Oral viscous budesonide (OVB) is quickly becoming the preferred therapy to fluticasone. The technique of swallowing a liquid dose may be more effective and efficient than “gulping” a hydrofluroalkane gaseous suspension. Additionally, OVB has comparable efficacy. One study found an 80% decrease in a symptom scoring index and regression of cell counts to less than 7 Eos/HPF; after 3 months of therapy there was decreased fibrosis/remodeling from baseline.

Dosing for fluticasone ranges from 220 to 880 μg per day, and for budesonide, from 0.5 to 2 mg per day; both doses are similar to those used in asthma. With either agent, patients are instructed to not eat or drink for 30 minutes after administration. Complications from topical treatment include oral/esophageal candidiasis.  In a 3-year case series studying recurrence, approximately 90% of adults relapsed at a mean of 8 months post discontinuation of 6 weeks of therapy. Just like asthma, when you stop using the controller medication, symptoms will come back.  No study of optimal dose or duration of therapy has been performed, but most adult providers recommend a 6-week course while pediatric providers suggest a 12-week course.  No long-term safety data exist pertaining to bone or adrenal effects from such small but more readily bioavailable dosing methods used in EoE.

Acid Suppression

Technically, EoE should not be diagnosed until response to PPI therapy has been determined, according to the 2007 and 2011 consensus guidelines. A certain subset of patients will have PPI-responsive esophageal eosinophilia.  Typically, dosing is either 10-40 mg omeprazole or 15-30 mg lansoprazole per dose for 2-3 months. High-dose PPI therapy may distinguish GERD from EoE.

Immunomodulating Therapy

Immunomodulating therapies may offer some promise. The best studied therapy is anti-IL-5. In mice, anti-IL-5 decreases blood and tissue eosinophils, and decreases eotaxin-3 levels. Garret and fellow researchers studied anti-IL-5 in 4 patients with hypereosinophilic syndrome. Symptoms and eosinophilia resolved, and in 1 patient who also had EoE, dysphagia and esophageal eosinophils decreased. Stein and colleagues, in an open-label phase I study of anti-IL-5, noted that blood eosinophilia was reduced but not correlated to decreased levels of IL-5, eotaxin-3, or esophageal eosinophilia.   Similarly, there was no significant difference between groups in symptom improvement. Studies of other agents, such as anti-IgE or anti-TNF (infliximab), failed to demonstrate any symptomatic or esophageal histologic improvement. Presently, anti-IL-3 is under investigation in a phase 1 trial, but no data are available pertaining to its safety or efficacy.

Dilation

Dilation relieves critical esophageal narrowing and related symptoms, but will not alter the underlying pathophysiology. Its benefit is maximized for dysphagia and impaction from ring/stricture or other critical narrowing. Several studies have demonstrated the efficacy of dilation, though it is balanced by risks including perforation, deep mucosal tears, pain, linear renting, and bacteremia. Relief is also likely to be transient, because 75%-50% of patients who receive this therapy have recurrence at 2-20 months and need additional dilation.

Dietary Management

A 6-week trial of 10 patients conducted by Kellyand colleagues in 1995 demonstrated the role of an exclusively elemental diet.  At the conclusion of the study, 8/10 had complete histologic and symptomatic resolution and the other 2 subjects showed drastic improvement, demonstrating an elemental diet as a potential treatment. As with steroid therapy, however, upon discontinuation, all patients relapsed. A larger study of elemental diet therapy in 51 patients was conducted by Markowitz and colleagues.  The researchers noted symptomatic response by 8 days and normalization in biopsy by 1 month in 49 of the patients studied. Liacouras and colleagues followed 389 patients with EoE over 10 years, 160 whom were treated with elemental diet and noted a 97% response rate to the diet and biopsy counts that were comparatively lower than 75 patients on swallowed fluticasone. Though exceptionally effective, elemental therapy is limited in that a patient’s only source of nutrition is a very specific hypoallergenic formula. This may not be appropriate for adolescents or adults. Some cases require placement of gastrostomy tube to assist with feeding.

An alternative approach is a tailored/guided diet that avoids only an individual’s known food sensitizations based on skin prick and/or patch testing. Spergel and colleagues described 120 patients placed on a guided elimination diet based on allergen testing.  After 6-8 weeks, 112 had near complete tissue resolution, though 39 relapsed upon reintroducing eliminated foods. In this cohort, 77% had at least 1 positive prick skin test, and 85% had 1 positive atopy patch test. Prick skin tests were most commonly positive to milk, egg, soy, and peanut. The foods that were most commonly positive to atopy patch test were corn, soy, wheat, and milk. Most patients were sensitized to multiple foods, and dietary nonresponders had more sensitizations than responders. Positive predictive value and negative predictive value for 13 commonly positive foods in EoE were published in a previous post.

Follow-up of patients with EoE should be frequent, at least 4 times per year, with consideration for repeat endoscopy at those intervals as well. Repeat endoscopy is the only way to monitor disease progress, because symptoms do not always correlate with disease progression. One pediatric study found that an initial cell count of 6 or greater was predictive of a repeat positive biopsy.

 At each follow-up visit, diet should be reviewed, diet/medication compliance assessed, and consideration given for additional food testing if symptoms or histology are not improving. As noted previously, there are no studies that have evaluated adequate or optimal duration of treatment for either dietary avoidance or topical steroid duration. Very little formal guidance is available to determine key long term predictors of disease resolution, the optimal interval for repeat biopsy, and the effect of these factors on the development of long term sequelae.

Complications from EoE include:

  • Strictures,
  • Schatzki ring
  • Esophageal trachealization and stretching,
  • Esophageal furrowing and narrowing, microabscesses, webbing,
  • Food impaction, persistent/progressive dysphagia, and lamina propria fibrosis.

Esophageal remodeling in EoE occurs as a result of subepithelial fibrosis and is reported in 15%-40% of affected adults. Predictors that influence the likelihood of developing fibrosis are presently unknown. To date, there is no identified association with progression to malignancy directly from the presence of EoE. Some have observed a potential link between celiac disease and EoE, which may share some common gene upregulations with EoE, but this association is not well understood.

The natural history of food allergy/sensitization within EoE has not been well-described. Lastly, while preliminary work and observation indicates that quality of life can be affected significantly, little formal study of EoE quality of life exists. This particular area of research is very important to continue to define, as the quality of life issues that affected families face are distinct from those of the general food allergy community.

From the Journal of Allergy & Clinical Immunology (In Practice)

 Informational video on eosinophilic conditions

The More You Know, the Less You Know

The practice of medicine is just that….I advise the recommended treatment based on the information available at the time.  If I look back to the time during my fellowship in the early 90’s, much of what we thought was true and now 20 years later, been disproven.  As an example, the following study from a respected medical journal cautions against the use of PPI medication for reflux in children.  It’s worth your attention, but first some background information.

Children have a high prevalence of asthma and gastroesophageal reflux (GER). Children with asthma often report symptoms of GER and also have a high prevalence of asymptomatic GER.  We call this “silent reflux”. 

Some experts have suggested that untreated GER may cause persistent asthma control problems in children refractory to treatment with inhaled corticosteroids. However, whether treatment with proton pump inhibitors (PPIs) improves asthma control has not previously been determined. The objective of this study by Holbrook and colleagues was to determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.  (ie, Prevacid for “silent reflux”)

Study Synopsis and Perspective

Use of PPIs in children with poorly controlled asthma who were using inhaled corticosteroids and who had no symptoms of GER was not found to improve asthma control and was, in fact, associated with an increase in adverse effects, according to results of a study published in the January 25 issue of JAMA. (PPIs Produce Negative Outcomes in Children With Poor Asthma Control)

PPIs “are often prescribed for poorly controlled asthma regardless of reflux symptoms, and there have been large increases in the use of PPIs among children between 2000 and 2005…. Hence, it is of clinical importance to determine whether antireflux therapy, the most common of which are PPIs, improves control of asthma in children,” write Janet T. Holbrook, MPH, PhD, from the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and colleagues from the Writing Committee for the American Lung Association Asthma Clinical Research Centers.

The goal of this placebo-controlled, double-masked, randomized study was to determine whether the PPI lansoprazole was effective in controlling asthma symptoms in children with asthma, but no overt GER. The researchers also investigated whether pH testing would identify children with GER who responded to PPI therapy.

The children were randomly assigned to receive either lansoprazole (15 mg/day for those weighing <30 kg; 30 mg/day for those weighing ≥30 kg; n = 149) or a matching placebo (n = 157). The researchers found that the mean difference in the Asthma Control Questionnaire (ACQ) score between the 2 groups was 0.2 units (95% confidence interval [CI], 0.0 – 0.3 units), which was not statistically significant (P = .12).

There also was no significant difference in the forced expiratory volume in the first second (FEV1; 0.0 L; 95% CI, −0.1 to 0.1 L), and no change in the rate of episodes of poor asthma control (relative risk [RR], 1.2; 95% CI, 0.9 – 1.5) or asthma-related quality of life (−0.1; 95% CI, −0.3 to 0.1). In addition, children treated with lansoprazole developed more respiratory infections (RR, 1.3; 95% CI, 1.1 – 1.6; P = .02) than those in the placebo group.

A subgroup of children in the study (n = 115) underwent esophageal pH studies before randomization; the prevalence of GER among this group was found to be 43%. In those children with a positive pH study, there was no positive treatment effect with lansoprazole vs placebo for any asthma outcome.

The most common adverse event reported among both groups was asthma exacerbation.

  • This is the exact opposite of what I would expect!

A higher prevalence of upper respiratory tract infections, sore throats, and episodes of bronchitis was noted among patients in the lansoprazole group. The study authors speculate that this may be a result of loss of host defense against bacterial colonization as a result of higher gastric pH levels.

“The results of this clinical trial are uniformly negative regarding the benefit of acid suppression therapy on symptom relief, lung function, airway reactivity, or quality of life,” write the authors. The results also “indicate that PPI therapy for poorly controlled asthma is not warranted.”

In an accompanying editorial, Fernando Martinez, MD, from the Arizona Respiratory Center, University of Arizona, Tucson, notes that although it is not a statistically significant difference, the increase in activity-related bone fractures in the lansoprazole group also raises concerns. This potential complication has prompted an advisory from the US Food and Drug Administration about the risk for fractures in adults receiving chronic PPI therapy.

Overall, however, Dr. Martinez praises the work of Dr. Holbrook and colleagues and concludes that “[g]iven their potential adverse effects, these medications should thus be used with great restraint for treatment of GER/[gastroesophageal reflux disease] during childhood. The substantial increase in use of PPIs in children during the last decade is worrisome and unwarranted.”

Support for this study was provided by the American Lung Association Asthma Clinical Research Centers Infrastructure Award and National Institutes of Health/National Heart, Lung, and Blood Institute grants. Dr. Holbrook and colleagues have disclosed no relevant financial relationships. Dr. Martinez has served as a consultant to MedImmune and has presented at an Abbott-sponsored seminar.

JAMA. 2012;307:373-381, 406-407.

Study Highlights

  • The Study of Acid Reflux in Children With Asthma was a randomized, masked, placebo-controlled, parallel clinical trial comparing lansoprazole vs placebo in children without overt GER but with poor asthma control despite treatment with inhaled corticosteroids.
  • Lung function measures, such as FEV1, asthma-related quality of life, and episodes of poor asthma control, were secondary endpoints.
  • In the subgroup with a positive pH study result, there was no apparent treatment effect for lansoprazole vs placebo for any asthma outcome, including asthma-related quality of life or lung function.
  • Lansoprazole was also ineffective in subgroups defined by markers of asthma severity (either FEV1 at baseline or oral corticosteroid use in the past year).
  • At least 1 serious adverse event occurred in 10 participants in the lansoprazole group and 9 in the placebo group.
  • Asthma exacerbation was the most common serious adverse event in both groups (15 of 25 reports).
  • The investigators concluded that in children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole did not reduce symptoms or improve lung function but was associated with increased adverse events.
  • The findings do not support routine esophageal pH testing to identify children who respond to PPIs, nor do they support trials of PPIs for poorly controlled asthma.
  • An accompanying editorial notes that the overuse of PPIs in childhood asthma is an example of “therapeutic creep,” or extending the use of a treatment with real or suggestive therapeutic effects in selected patients to other patients in whom the efficacy of that treatment has never been demonstrated.
  • The editorial also notes that therapeutic creep increases the risk for potential adverse effects without any added advantage for patients and may have significantly added to the marked increase in asthma drug costs.

Clinical Implications

  • Findings of a randomized, placebo-controlled trial suggest that PPI treatment of children with poorly controlled asthma but without symptomatic GER is not effective in reducing asthma symptoms or improving lung function.
  • In this randomized, placebo-controlled trial, the addition of lansoprazole was associated with increased adverse events, particularly respiratory tract infections. There may be significant safety concerns for long-term PPI use in children, meriting further research
  • I personally wonder if more aggressive use of Vitamin D replacement would be helpful for the increase in risk of fractures for the patients taking PPI medication.  Yes indeed, further research is warranted. 

Full reference on the dangers of PPI medications

Breaking News on fainting spells after exercise–Allegra or Zantac responsible?

Medications for Allergies and Acid Reflux Can Cause Fainting After Working Out

By Rebecca Bardelli, Yahoo! Contributor Network 1 hour, 57 minutes ago

 

As always, this type of a study needs confirmation, but it got my attention!  Many patients take Allegra & Zantac on a regular basis and give no thought to exercise.  Here’s an article summary (be careful):

If you take medication for allergies or acid reflux, you should be aware that some medications in that class have been connected to post-workout fainting.

 

Zantac and Allegra are two brands of medications that can cause fainting after exercise.
Wikimedia Commons/Michelle Tribe

The studies

Several studies led researches to find that two regularly used medications can greatly lower low blood pressure after vigorous physical activity when they are used beforehand. These medications worked by stopping post-exercise hyperemia, a boost in the flow of blood that occurs in the muscles that are connected to the skeleton during the crucial hour and a half recovery time that happens after working out. All together, taking these medications before physical activity caused a reduction in the blood flow that normally occurs post-exercise by 80 percent. 

Losing consciousness after exercising is a health problem known as syncope. This condition can be a sign of an acute heart condition, but most times it is related to a drop in blood pressure and a decreased flow of blood to the brain.

John R. Halliwill, the principal investigator, says, “There is reason to believe that histamine is the primary vasodilator contributing to post-exercise hypotension, but we cannot say for certain.” Halliwill is a professor of human pysiology, and he went on to say, “Some people have problems regulating blood pressure during and after exercise. Trained athletes have had fainting bouts at the end of exercise. It may be that these result from a natural overactivation of these two receptors for histamine.”

 The study funded by the American Heart Association involved people who did not have high blood pressure and were non-smokers.

 Where do you find the medications in question: look below

Fexofenadine

 One of the medications mentioned in the studies is fexofenadine, also known as: 

*Allegra

*Wal-Fex

*Allegra-D 12 Hour (containing Pseudoephedrine and fexofenadine)

*Allegra-D 24 Hour (containing Pseudoephedrine and fexofenadine)

*Wal-Fex D (containing Pseudoephedrine and fexofenadine)

 Other side effects of fexofenadine that may interfere with exercise include:

*Diarrhea

*Dizziness

*Generalized pain, or pain in the arms, back or legs

*Headaches

*Menstrual discomfort in females

*Throwing up

 This medication is used to treat allergies.

 Ranitidine

 Rantidine is the other medication refereed to in the studies. This medication is also known by the names:

*Rx-Act Heartburn Relief

*Tritec

*Wal-Zan

*Zantac

 Other side effects of ranitidine that could interfere with exercise include:

*Constipation or diarrhea

*Headache

*An upset stomach or vomiting

 This medication is used to treat gastroesophageal reflux disease (GERD).

 Stay tuned for more info!

After Thanksgiving Hangover!

Treating Acid Reflux Disease With Diet and Lifestyle Changes

 Need I say more?

Recipe for heartburn!

Do you often experience the pain of heartburn or other symptoms of acid reflux disease? Most patients despise yet another medication to treat reflux.  You might take comfort in knowing that making diet changes as well as other lifestyle changes may be all you need to do. Here’s how. (the above links to WebMD can be trusted)

What Kind of Diet Changes Can Help Acid Reflux?

One thing you can do to reduce your risk for heartburn and acid reflux disease is to eat low-fat, high-protein meals. Also, eat smaller meals more frequently; eat until you’re no longer hungry–avoid eating until you feel full.  You will always eat less if you eat slower; your mother was correct! 

Mother is usually right!

It may also help to avoid certain beverages and foods.

Avoid beverages that seem to trigger heartburn or make it worse, such as:

  • Coffee or tea (both regular and decaffeinated)
  • Other beverages that contain caffeine
  • Carbonated beverages
  • Alcohol

Avoid foods that seem to trigger your heartburn or make it worse, such as:

  • Citrus fruits, such as oranges and lemons
  • Tomatoes and products that contain tomatoes, such as tomato sauce and salsa
  • Chocolate
  • Mint or peppermint
  • Fatty or spicy foods, such as chili or curry
  • Onions and garlic

What Other Lifestyle Changes Can Treat Acid Reflux?

In addition to acid reflux diet changes, see which of the following lifestyle changes you can make.

  • Quit smoking . Smoking may increase your risk for heartburn and acid reflux disease in many ways. For example, it may increase the amount of acid secreted by your stomach and interfere with the function of muscles that help keep acid down.
  • Reduce reflux while sleeping.These steps will help reduce reflux when you sleep:
    • Put blocks under the head of your bed to raise it at least 4 to 6 inches. This helps keep your stomach’s contents down. However, it doesn’t work to simply use lots of extra pillows because this position may increase pressure on your abdomen.
    • Stop eating at least two or three hours before lying down.
    • Try sleeping in a chair for daytime naps.
  • Lessen the pressure.Often, extra pressure around your abdomen increases acid reflux. Try these steps:
    • Don’t wear tight clothes or tight belts.
    • If you’re overweight or obese, take steps to lose weight with exercise and diet changes.  Here again, WebMD has some great tips to get started.

Can Medication Help Heartburn?

Over-the-counter medications can help neutralize stomach acid. Be careful at this point.  Antacids and ranitidine (called Zantac™) are very weak–I would recommend starting with Prilosec™ or omeprazole. Use 20mg morning and evening until symptoms are well-controlled.  Antacids may give quick, short-term relief for many people, but it doesn’t take care of the “root” of the problem, that is oversecretion of acid from the stomach.  If you find you need to keep taking OTC meds  for more than two weeks, see your doctor or other health care provider.

Also, ask your doctor whether any medication could be triggering your heartburn or other symptoms of acid reflux disease. These are examples of medications that may trigger acid reflux:

  • Aspirin or NSAIDs, such as Motrin
  • Some muscle relaxants
  • Certain blood pressure drugs

Want more information on GERD or heartburn?  Look no further–AAAAI!